The major objectives of the proposal are the development of rapid tests for urinary bladder carcinogens and the prevention of bladder cancer in man by the use of protease inhibitors. The detection of bladder carcinogens will help environmental hazards in commercial dyes and the nature of the proximal carcinogens. Progress has been made in the understanding of mutations in microorganisms. The mutations appear to be due to error prone repair of DNA. This repair is induced when DNA is damaged and is incapable of supporting division. The induction is inhibited by protease inhibitors, and carcinogenesis is inhibited by protease inhibitors. We will apply this technique to urines of experimental animals fed dyes and other possible bladder carcinogens. We hope to apply this technique to urines of men possibly exposed to carcinogens as well. We will continue our work in preventing bladder cancer in Fisher rats fed (N-4-5-nitro-2-furyl)2-thiazolyl formamide (FANFT) with protease inhibitors and cortical steroids; and N-butyl-(4-hydroxy-butyl)-nitrosamine (BBN). Moreover, we will test cis-retinoic acid as inhibitor of bladder carcinogenesis in this animal model experiment.